Head Tail

T1 T2 T3 A1 A2 A4 A5 A6 A7A3

A8

Metamorphosis

Quiltwork Assembly of a Fly

Outline of Vein DevelopmentM L1

L2

L3

L4

L5

3rd Larval Instar

Early Pupa

ML1 L2

L3

L4

L5

L6

sCo

Mid-Pupa->Adult

L1

L2

L3

L4

L5

M

Fly Wing

The Players: A/P Axis

Engrailed (En) = Transcription factor expressed in posterior cells.

Hedgehog (Hh) = Signal whose expression is activated by En.

Dpp = Signal whose expression is activated by Hh signaling.

Sal = Transcription factor activated by Dpp signaling.

L2

L3

L4

L5

sal

Determining the Positions of Veins

hh

L2

dpp

dppAP En

En -> Hh -> Diffuses -> dpp in A/P Organizer

Dpp

Dpp -> Diffuses -> sal -> L2 vein

AP

L5

sal

sal

L3

L4

L3

L4

OrganizerA/P

dpp

L2

L3

L4

L5

hh- mutantL2

L3L4

L5

WTL2

L3

L4

L5

Hh Determines Positions of L3 and L4 Veins

hh dpp

dppAP En

L3

L4

En -> Hh -> Diffuses ->dpp in A/P Organizer

hh

dpp

Mutant with reduced hh function

AP En

L3L4

dpp

dpp- mutant

L2

L3

L4

L5

L2

DppAP

L5

salL3

L4sal

Mutant with reduced dpp function

WTL2

L3

L4

L5

L2

DppAP

L5

sal

sal

L3

L4

Dpp -> Diffuses -> sal -> L2 vein

Dpp Determines Positions of L2 and L5 veins

Veins Form At Boundaries Along the A/P Axis

L2L3 L4

salsal Dpp

A P

Dpp -> Diffuses -> sal -> L2 vein

L5

+

En

hh

dpp

+

dpp

A P

OrganizerA/P

En -> Hh -> Diffuses ->dpp in A/P Organizer

salsal Dpp

A P

Dpp defines anteriorborder of sal domain

+

En

hh

dpp

+

dpp

A P

En-5 defines position ofdpp stripe in wing disc

Hb

eve-3

Hb defines anteriorborder of eve-3 stripe

KniWingDisc

en-5

Eve-3 defines anteriorborder of en-5 stripe

Maternal Bicoid gradientdefines posterior limit of hb

Ant. Post.

Lowest level of Bcd needed to activate hb

Sal defines positionof L2 vein stripe

salDpp

++

Sal

L2

X

L2 A P

The Developmental Path From Bcd to the L2 Vein

The Players: D/V and P/D Axes

Apterous (Ap) = Transcription factor expressed in dorsal cells.

Notch (N) = Signaling system that induces margin at D/V border.

Distalless = Transcription factor activated at A/P & D/V intersection.

D ->V Signal

V -> D Signal

ap Expressing Cells

ap Non-expressing Cells

DV

Activation ofNotch AlongFuture Margin

Ap -> Notch -> Wing Margin = D/V Organizer

D/V Signaling Is Required for Wing Margin Formation and Wing Outgrowth

D/V Organizer -> Margin Formationand Wing Growth

ap- cells

Wing imaginal disc in larva Adult wing (viewed end on) Adult wing with ap- patch

Loss of ap in Dorsal Cells-> Margin Formation

Intersection of the D/V and A/P Organizers Induces Leg Outgrowth

D/V Organizer

A P

A/P Organizer

DistallessExpression

Distalless

Distal

Proximal

Normal Leg distallessMutant Leg

DV

Fig. 4.4

Hox2

ZPA Morphogen = Hh

FGF

Hox Gene B

ZPA induced byHox gene B + FGF

FGF and a second Hox gene activate Hh expression in ZPA

wing bud leg bud

FGF

Hox Gene A Hox Gene CHox Gene B

GastrulatingChicken Embryo

FGF

Hox genes activate autoregulatory FGF expression in limb buds

Initiation of Wing Development in Chickens

A PGrafted ZPA

[Hh]

distanceAnt. Post.

4

32 2

3

4

43

2

43

2

ZPA -> HhBMP-4

A P

[Hh]

distanceAnt. Post.

4

32 43

2Anterior

Posterior

43

22

A PFraction ofZPA Grafted

4

[Hh]

distanceAnt. Post.

32 2

Hh diffuses from ZPA and specifies digits 2-4 at different concentrations

Wing bud with second grafted ZPA -> complete mirror duplicated digits

Wing bud grafted with a fraction of ZPA -> partial mirror duplication

Hh is the ZPA Factor

Normal Wing

ZPA Transplant

ZPA Graft

0 mg/ml

4 mg/ml

8 mg/ml

16 mg/ml

Hh Soaked BeadsHh Expression

ZPA

A P/

Hh

Dpp

Hh Hh

BMP-4

A P

Fly wing disc

A/PAxis

Vertebrate Limb Bud

D/VAxis

P/DAxis

D

V

A P

NotchSignaling A P

DV

NotchSignaling

D

V

A P

Distalless

A P

DV

Distalless